The need for reliable methods that furnish alkenes efficiently and stereoselectively continues to represent a difficult and most compelling challenge in the field of chemical synthesis. Protocols that are catalytic or deliver thermodynamically less favored Z alkenes are particularly scarce. Olefin synthesis through Wittig-type protocols is one of the more commonly used procedures for accessing cis disubstituted olefins; such transformations, however, require stoichiometric amounts of arylphosphonium salts, leading to notoriously low degrees of atom economy and, at times, complicated and costly purification procedures. Catalytic hydrogenation of alkynes is another established route that leads to Z olefins. Synthesis of the requisite substrates is, however, not always straightforward, reactions require catalysts that are based on expensive precious metals (e.g., Pd-, Pt-, or Rh-based) and a lead-based component (e.g., Pb(OAc)2), over-reduction is often a concern (separation of the desired alkene and the adventitious alkane is typically not straightforward).
Catalytic olefin metathesis has transformed chemical synthesis and offers exceptionally efficient pathways for synthesis of alkenes. Among various types of olefin metathesis, cross-metathesis of two different terminal alkenes, a reaction that generates only the easily removable ethylene as the side-product, constitutes a remarkably attractive and efficient strategy for synthesis of disubstituted alkenes. Cross-metathesis, however, is a mechanistically complicated variant of this class of transformations. In ring-closing metathesis, reacting alkenes are tethered and the intramolecular reaction is favored; in ring-opening metathesis, release of strain typically serves as the driving force that results in one of several pathways to be preferred. In contrast, cross-metathesis demands that two different alkenes react without the entropic benefit of an intramolecular reaction or strain release, and under conditions that can also cause homo-coupling of the cross partners. What often renders the goal of a Z-selective cross-metathesis process a daunting challenge is that in the case of the large majority of related reactions reported thus far, the large majority of which are promoted by Ru-based carbenes, the energetically favored E olefin products are formed either predominantly or exclusively. It should be noted that early studies demonstrated that styrene and a variety of terminal alkenes undergo cross-metathesis in the presence of 1-5 mol % of an achiral Mo bis-alkoxide. Transformations were found to be highly E-selective (81% to >98% E). Only when acrylonitrile is used instead (vs. styrene) Z alkene products are formed predominantly (75-88% Z).
A great number of biologically active molecules and polymeric materials contain olefins; many reactions in organic chemistry require alkenes as starting materials. Disubstituted alkenes can exist as E or Z isomers, each possessing a unique geometry and distinct energetic attribute. Molecules with E or Z alkenes might exhibit different reactivity, selectivity and/or binding profiles with biological receptors. Methods that are catalytic and allow for stereoselective formation of olefins are therefore of considerable value. Such protocols are, however, relatively uncommon. Particularly scarce are efficient catalytic procedures for stereoselective synthesis of the higher energy Z alkenes.
Accordingly, there remains an unmet need for methods and catalysts for Z-selective cross metathesis reactions.